Evaluation of SARs for the prediction of skin irritation/corrosion potential - structural inclusion rules in the BfR decision support systemf

摘要

The German Federal Institute for Risk Assessment (BfR) has developed a Decision Support System (DSS) to assess certain hazardous properties of pure chemicals, including skin and eye irritation/corrosion. The BfR - DSS is a rule-based system that couldbe used for the regulatory classification of chemicals in the European Union. The system is based on the combined use of two predictive approaches: exclusion rules based on physicochemical cut-off values to identify chemicals that do not exhibit a certain hazard (e.g., skin irritation/corrosion), and inclusion rules based on structural alerts to identify chemicals that do show a particular toxic potential. The aim of the present study was to evaluate the structural inclusion rules implemented in the BfR-DSS for the prediction of skin irritation and corrosion. The following assessments were performed: (a) a confirmation of the structural rules by rederiving them from the original training set (1358 substances), and (b) an external validation by using atest set of 200 chemicals not used in the derivation of the rules. It was found as a result that the test data set did not match the training set relative to the inclusion of structural alerts associated with skin irritation/corrosion, albeit some skinirritants were in the test set.